-- Men who received 177Lu-PSMA-617 plus best standard of care had a 38% 
      reduction in risk of death (median OS benefit of 4 months) and a 60% 
      reduction in the risk of radiographic disease progression or death 
      (median rPFS benefit of 5 months) compared to best standard of care 
      alone1 
 
 
   -- Significant improvement demonstrated in all key secondary endpoints, 
      including time to first symptomatic skeletal event, overall response rate 
      and disease control rate1 
 
 
   -- VISION study findings to be presented during 2021 ASCO plenary; 
      regulatory submissions to US and EU Health Authorities on track for 2H21; 
      two additional pivotal studies in earlier lines of treatment for 
      metastatic prostate cancer to start 1H21, goal to move into earlier 
      stages of disease 
 
 
   -- Novartis commitment to leadership in radioligand therapy (RLT) further 
      strengthened by recent partnerships and investments; more than 15 ongoing 
      research and discovery programs to identify and accelerate next wave of 
      RLTs for cancer 
 
 
   Basel, June 3, 2021 -- Novartis today announced that results of the 
Phase III VISION study evaluating (177) Lu-PSMA-617, a targeted 
radioligand therapy, plus best standard of care (SOC) demonstrated 
significant improvement in overall survival (OS) compared to SOC alone, 
in patients with progressive PSMA-positive metastatic 
castration-resistant prostate cancer (mCRPC)(1) . The difference in OS 
between study arms was statistically significant (one-sided p<0.001), 
with an estimated 38% reduction in risk of death in the (177) 
Lu-PSMA-617 arm (n=551) compared to the best standard of care only arm 
(n=280) (hazard ratio: 0.62 with 95% confidence interval (CI): (0.52, 
0.74))(1) . These results will be presented during the 2021 American 
Society of Clinical Oncology (ASCO) Annual Meeting plenary session on 
June 6. 
 
   Patients receiving (177) Lu-PSMA-617 also demonstrated a statistically 
significant (one-sided p<0.001) 60% risk reduction for radiographic 
progression-free survival or death (rPFS), compared to the best standard 
of care only arm (hazard ratio: 0.40 with 99.2% CI: (0.29 0.57))(1) . 
There was a higher rate of drug-related treatment emergent adverse 
events reported in the (177) Lu-PSMA-617 treatment arm (85.3%) compared 
to standard of care alone (28.8%)(1) . 
 
   Across both arms of the study, rates of treatment discontinuation 
associated with treatment-emergent adverse events occurred as follows: 
In the (177) Lu-PSMA-617 plus standard of care (SOC) arm, 11.9% of 
patients discontinued (177) Lu-PSMA-617 and 8.5% discontinued SOC; while 
in the SOC alone arm 7.8% of patients discontinued treatment(1) . 
 
   "Patients suffering from metastatic CRPC who have progressed through 
contemporary hormonal treatments and chemotherapy have few meaningful 
therapeutic options," said Michael J. Morris, MD, who chaired the 
study's Scientific Committee and is the Prostate Cancer Section Head, 
Genitourinary Oncology Service, Division of Solid Tumor Oncology at 
Memorial Sloan Kettering Cancer Center. "The study demonstrated that 
(177) Lu-PSMA-617 improves disease progression and prolongs survival, 
which are key measures of clinical benefit in the mCRPC population. I am 
grateful to be a part of this study that may lead to additional 
therapeutic options for these patients." 
 
   "Men with metastatic prostate cancer have an approximately 3 in 10 
chance of surviving 5 years(2) . These data from the first Phase III 
study of a radioligand therapy in this advanced prostate cancer setting 
confirm the potential of (177) Lu-PSMA-617 targeted therapy to improve 
clinical outcomes," said John Tsai, Head of Global Drug Development and 
Chief Medical Officer for Novartis. "Our comprehensive development 
program for this targeted therapy seeks to reach eligible patients with 
advanced prostate cancer, who express the PSMA biomarker(1,) (3-6) . And, 
we won't stop with prostate cancer, our team is exploring next 
generation RLT across a number of tumor types." 
 
   Two additional studies with (177) Lu-PSMA-617 radioligand therapy in 
earlier lines of treatment for metastatic prostate cancer are planned to 
start in the first half of 2021, investigating potential clinical 
utility in the mCRPC pre-taxane setting (PSMAfore) and in the metastatic 
hormone-sensitive setting (PSMAddition). 
 
   Additional VISION data 
 
   Median OS (95% CI) for the (177) Lu-PSMA-617 plus best standard of care 
arm in the VISION study was 15.3 months (14.2, 16.9), compared to 11.3 
months (9.8, 13.5) in the best standard of care arm only(1) . The median 
rPFS (99.2% CI) was 8.7 months (7.9, 10.8) for the (177) Lu-PSMA-617 arm 
compared to 3.4 months (2.4, 4.0) for the best standard of care only 
arm(1) . 
 
   Key secondary endpoints were also met. The median time to first 
symptomatic skeletal event was 11.5 months (95% CI: 10.3, 13.2) in (177) 
Lu-PSMA-617 arm compared to 6.8 months (95% CI: 5.2, 8.5) in the best 
standard of care only arm (hazard ratio: 0.50 (95%CI: 0.40, 0.62)); 
two-sided p-value: <0.001(1) . Significant differences were also seen in 
overall response rate in patients with measurable or non-measurable 
disease at baseline (29.8% partial or complete response in the (177) 
Lu-PSMA-617 arm compared to 1.7% partial response in the best standard 
of care only arm (two-sided p-value: <0.001)) and disease control rate 
(89.0% in (177) Lu-PSMA-617 arm compared to 66.7% in the best standard 
of care only arm (two-sided p-value: <0.001))(1) . 
 
   Grade >=3 drug-related treatment emergent adverse events occurred in 
28.4% of the (177) Lu-PSMA-617 arm compared to 3.9% in the best standard 
of care only arm(1) . The most common treatment emergent adverse events 
regardless of drug relatedness (above 2% respectively for the (177) 
Lu-PSMA-617 and best standard of care arm) were anemia (12.9% vs. 4.9%), 
thrombocytopenia (7.9% vs. 1%), lymphopenia (7.8% vs. 0.5%), fatigue 
(5.9% vs. 1.5%), urinary tract infection (3.8% vs 0.5%), neutropenia 
(3.4% vs 0.5%), hypertension (3.2% vs 1.5%), back pain (3.2% vs. 3.4%), 
acute kidney injury (3.0% vs 2.4%), leukopenia (2.5% vs. 0.5%), bone 
pain (2.5% vs. 2.4%), hematuria (2.5% vs 0.5%), and spinal cord 
compression (1.3% vs. 5.4%)(1) . 
 
   Serious drug-related treatment emergent adverse events occurred in 9.3% 
of patients in the (177) Lu-PSMA-617 arm compared to 2.4% in the best 
standard of care only arm(1) . 
 
   Visit https://www.hcp.novartis.com/virtual-congress/a-2021/ for the 
latest information from Novartis, including our commitment to the 
Oncology community, and access to our ASCO21 Virtual Scientific Program 
data presentations (for registered participants). 
 
   About Advanced Prostate Cancer 
 
   Prostate cancer is a form of cancer that develops in the prostate gland, 
a small walnut shaped gland in the pelvis of men. In castration 
resistant prostate cancer (CRPC), the tumor shows signs of growth, such 
as rising Prostate Specific Antigen (PSA) levels, despite the use of 
hormone treatments that lower testosterone(7) . In metastatic CRPC 
(mCRPC), the tumor spreads to other parts of the body, such as 
neighboring organs or bones and remains unresponsive to hormone 
treatment(7) . The five-year survival rate for patients with metastatic 
prostate cancer is approximately 30%(2) . 
 
   About Phenotypic Precision Medicine in Advanced Prostate Cancer 
 
   Despite advances in prostate cancer care, there is a high unmet need for 
new targeted treatment options to improve outcomes for patients with 
mCRPC. More than 80% of prostate cancer tumors highly express a 
phenotypic biomarker(6) called Prostate Specific Membrane Antigen (PSMA) 
(3-5) (,) (8-9) , making it a promising diagnostic (through positron 
emission tomography (PET) scan imaging) and potential therapeutic target 
for radioligand therapy(1) (0) . This differs from 'genotypic' precision 
medicine which targets specific genetic alterations in cancer cells(6) . 
 
   About (177) Lu-PSMA-617 
 
   (177) Lu-PSMA-617 is an investigational PSMA-targeted radioligand 
therapy for metastatic castration-resistant prostate cancer. It is a 
type of precision cancer treatment combining a targeting compound 
(ligand) with a therapeutic radioisotope (a radioactive particle)(1) (1) 
(-1) (3) . After administration into the bloodstream, (177) Lu-PSMA-617 
binds to prostate cancer cells that express PSMA(1) (4) , a 
transmembrane protein, with high tumor-to-normal tissue uptake(1) (1) (, 
1) (5) (,1) (6) . Once bound, emissions from the radioisotope damage 
tumor cells, disrupting their ability to replicate and/or triggering 
cell death(17-19) . The radiation from the radioisotope works over very 
short distances to limit damage to surrounding cells(1) (0) (,) (1) (1) 
(,1) (5) . 
 
   About VISION 
 
   VISION is an international, prospective, randomized, open-label, 
multicenter, phase III study to assess the efficacy and safety of (177) 
Lu-PSMA-617 (7.4 GBq administered by intravenous infusion every 6 weeks 
for a maximum of 6 cycles) plus investigator-chosen best standard of 
care in the investigational arm, versus best standard of care in the 
control arm(20) . Patients with PSMA PET-scan positive mCRPC, and 
progression after prior taxane and androgen receptor pathway inhibitors, 
were randomized in a 2:1 ratio in favor of the investigational arm(20) . 
The alternate primary endpoints were rPFS and OS(20) . The study 
enrolled 831 patients(1) . 
 
   Disclaimer 
 
   This media update contains forward-looking statements within the meaning 
of the United States Private Securities Litigation Reform Act of 1995. 
Forward-looking statements can generally be identified by words such as 
"potential," "will," "would," "anticipated," "believe," "committed," 
"commitment," "investigational," "evaluating," "promising," "ambition," 
"opportunity," "upcoming," "pursuing," "underway," "to ensure," "intend, 
" "to submit," or similar terms, or by express or implied discussions

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June 03, 2021 12:04 ET (16:04 GMT)